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Chemical structures of ( a ) methacrylated alginate modified with RGD-containing peptide and ( b ) methacrylated heparin.
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Nanofibrous scaffolds are of interest in tissue engineering due to their high surface area to volume ratio, interconnected pores, and architectural similarity to the native extracellular matrix. Our laboratory recently developed a biodegradable, photo-crosslinkable alginate biopolymer. Here, we show the capacity of the material to be electrospun in...
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... controlled cell adhesion and bioactive factor delivery. Here we report on the ability to electrospin the methacrylated alginate into nanofibres and crosslink the fibres using ultraviolet (UV) light to form stable nanofibrous scaffolds. The alginate polymer backbone can be covalently modified with cell-adhesive peptides to control cell adhesion (Fig. 1a). Methacrylated heparin (Fig. 1b) can be blended with methacrylated alginate so that upon crosslinking, the alginate scaffold will contain covalently linked heparin to mediate the sustained release of incorporated growth factors (Jeon et al., 2011). Both the peptides and the heparin remain bioactive following the electrospinning ...
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... factor delivery. Here we report on the ability to electrospin the methacrylated alginate into nanofibres and crosslink the fibres using ultraviolet (UV) light to form stable nanofibrous scaffolds. The alginate polymer backbone can be covalently modified with cell-adhesive peptides to control cell adhesion (Fig. 1a). Methacrylated heparin (Fig. 1b) can be blended with methacrylated alginate so that upon crosslinking, the alginate scaffold will contain covalently linked heparin to mediate the sustained release of incorporated growth factors (Jeon et al., 2011). Both the peptides and the heparin remain bioactive following the electrospinning process. The resultant nanofibres thus ...
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This chapter contains sections titled: Introduction Alginate: General Properties Extraction and Preparation Alginate Hydrogels Photocross‐Linking Shape‐Memory Alginate Scaffolds Biodegradation of Alginate Biomedical Application of Alginates
As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied...
Citations
... An in vitro degradation profile of BCP-6Sr2Mg2Zn, BCP-6Sr2Mg2Zn-PEU and BCP-6Sr2Mg2Zn-PCL scaffolds (~10 mm × 10 mm) with an average thickness of 2 mm was evaluated in α-MEM medium without ribonucleosides and deoxyribonucleosides (GIBCO™ Invitrogen Corporation, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (Cytiva HyClone™ Fetal Bovine Serum (FBS) U.S. Origin, Fisher Scientific, Loughborough, UK), 1% Penicillin/Streptomycin and 1% Amphotericin B (Gibco) at pH = 7.4, according to the method previously used by Jeong and co-workers [41]. Briefly, the dried scaffolds were immersed in the culture medium at a 1:10 ratio of scaffold weight (g) to solution volume (mL) in a constant temperature incubator shaker (37 • C, 100 rpm). ...
... The samples were washed gently with deionized water to eliminate non-adherent particles, dehydrated with absolute ethanol and dried in an oven (40 • C) to constant weight. The weight loss (%) at each time point was calculated using Equation (1) [41], ...
This study investigates the osteogenic differentiation of umbilical-cord-derived human mesenchymal stromal cells (hUC-MSCs) on biphasic calcium phosphate (BCP) scaffolds derived from cuttlefish bone doped with metal ions and coated with polymers. First, the in vitro cytocompatibility of the undoped and ion-doped (Sr2+, Mg2+ and/or Zn2+) BCP scaffolds was evaluated for 72 h using Live/Dead staining and viability assays. From these tests, the most promising composition was found to be the BCP scaffold doped with strontium (Sr2+), magnesium (Mg2+) and zinc (Zn2+) (BCP-6Sr2Mg2Zn). Then, samples from the BCP-6Sr2Mg2Zn were coated with poly(ԑ-caprolactone) (PCL) or poly(ester urea) (PEU). The results showed that hUC-MSCs can differentiate into osteoblasts, and hUC-MSCs seeded on the PEU-coated scaffolds proliferated well, adhered to the scaffold surfaces, and enhanced their differentiation capabilities without negative effects on cell proliferation under in vitro conditions. Overall, these results suggest that PEU-coated scaffolds are an alternative to PCL for use in bone regeneration, providing a suitable environment to maximally induce osteogenesis.
... Wound-healing, which is one of the most complicated processes, involves a series of events, such as cell response, growth, and differentiation [110]. Consequently, the products used for the treatment of wounds must be characterized by durability, nontoxicity, and flexibility. ...
Over the last two decades, bio-polymer fibers have attracted attention for their uses in gene therapy, tissue engineering, wound-healing, and controlled drug delivery. The most commonly used bio-polymers are bio-sourced synthetic polymers such as poly (glycolic acid), poly (lactic acid), poly (e-caprolactone), copolymers of polyglycolide and poly (3-hydroxybutyrate), and natural polymers such as chitosan, soy protein, and alginate. Among all of the bio-polymer fibers, alginate is endowed with its ease of sol–gel transformation, remarkable ion exchange properties, and acid stability. Blending alginate fibers with a wide range of other materials has certainly opened many new opportunities for applications. This paper presents an overview on the modification of alginate fibers with nano-particles, adhesive peptides, and natural or synthetic polymers, in order to enhance their properties. The application of alginate fibers in several areas such as cosmetics, sensors, drug delivery, tissue engineering, and water treatment are investigated. The first section is a brief theoretical background regarding the definition, the source, and the structure of alginate. The second part deals with the physico-chemical, structural, and biological properties of alginate bio-polymers. The third part presents the spinning techniques and the effects of the process and solution parameters on the thermo-mechanical and physico-chemical properties of alginate fibers. Then, the fourth part presents the additives used as fillers in order to improve the properties of alginate fibers. Finally, the last section covers the practical applications of alginate composite fibers.
... Alginate-based products are particularly suited for biomedical applications since they are biocompatible, biodegradable, and nonimmunogenic. Such constructs have been used in 2-D and 3-D cell culture as well as in drug delivery and wound healing applications [1][2][3][4][5][6]. ...
Electrospinning natural polymers represents a developing interest in the field of biomaterials. Electrospun nanofibers have been shown to facilitate tissue regeneration and emulate body tissue, making them ideal for modern biomedical applications. These water-soluble natural polymers including alginate, have also shown promise as drug delivery vehicles. However, many biopolymers including alginate are inherently charged, making the formation of nanofibers difficult. To better understand the potential of natural polymer-based fibers in drug delivery applications, fiber formulations and drug loading concentrations of alginate-based scaffolds were investigated. It was found electrospinning poly(vinyl alcohol) with alginate facilitated fiber formation while the co-polymer agarose showed minor improvement in terms of alginate electrospinnability. Once uniform fibers were formed, the antibiotic ciprofloxacin was added into the polymer electrospinning solution to yield drug-loaded nanofibers. These optimized parameters coupled with small molecule release rate data from the drug-loaded, alginate-based fibers have been used to establish a catalog of small molecule release profiles. In the future, this catalog will be further expanded to include drug release rate data from other innately charged natural polymer-based fibers such as chitosan. It is anticipated that the cataloged profiles can be applied in the further development of biomaterials used in drug delivery.
... Based on this, Yoon et al. modified heparin with N-methylacrylamide hydrochloride and then crosslinked it with cryloylmodified Pluronic F127 to obtain composite hydrogels for the controlled release of growth factors [57]. Jeong et al. successfully prepared electrospun fiber scaffolds by mixing methyl acrylate-modified alginate and methyl acrylate-modified heparin with polyoxyethylene (PEO) through electrospinning and photocrosslinking, and found that they were effective inregulating cell behavior (Figure 1d) [52]. ...
... (c) Synthetic roadmap for cinnamoyl chloride chloride-modified[51]. (d) Structural formula of heparin modified by methyl acrylate[52]. ...
Hydrogel materials have great application value in biomedical engineering. Among them, photocrosslinked hydrogels have attracted much attention due to their variety and simple convenient preparation methods. Here, we provide a systematic review of the biomedical-engineering applications of photocrosslinked hydrogels. First, we introduce the types of photocrosslinked hydrogel monomers, and the methods for preparation of photocrosslinked hydrogels with different morphologies are summarized. Subsequently, various biomedical applications of photocrosslinked hydrogels are reviewed. Finally, some shortcomings and development directions for photocrosslinked hydrogels are considered and proposed. This paper is designed to give researchers in related fields a systematic understanding of photocrosslinked hydrogels and provide inspiration to seek new development directions for studies of photocrosslinked hydrogels or related materials.
... Nanofiber characterization, cell interaction, adhesion and proliferation, binding and releasing heparin tests [28,96] 4 wt % Na ALG-5 wt % PEO-0.5 wt % Triton X-100-5 wt % DMSO; Na ALG/PEO ratios: 65 [11,42,89,98,99] AgNO 3 -6% Ca ALG fibers Antimicrobial effect [11,89,98,100] 0.5-0.75% w/v Chitosan-0.5-1% w/v ALG-Dexamethasone/BSA/PDGF-bb/Avidin fibers Drug incorporation and release, PDGF-bb bioactivity [49,90] 0, 0.014, 0.041% w/v Chitosan-0.001% w/v Na ALG-Ninhydrin-CaCl 2 in fibers Filament characterization [49,101] 1.5 w % Na ALG-Ag-NPs in crosslinked fibers Wound healing effect on SKH-1 mice [102] An uniform morphology of the nanofibers can also be obtained by adding lecithin as a natural surfactant [93], or arginine-glycine-aspartic acid (RGD) [103]. ...
... The resulting photo-cross-linked nanofibers can also be coated with gold. Before the cross-linking the fiber diameters were between 185.5 ± 37 and 195.4 ± 23 nm, after cross-linking the fiber diameters were between 182.2 ± 36 and 190.4 ± 30 nm, but the PEO extraction lead to a diameter increase due to nanofiber swelling, ranging between 256.3 ± 43 and 297.9 ± 42 nm [96]. When this study used PEO/methacrylated heparin-, RGD-modified-, or unmodified methacrylated alginate-based nanofibers, it concluded that-by adding methacrylated heparin-the stress-strain curves are influenced, therefore making the elongation at break significantly lower and the tensile strength and Young's modulus significantly greater than those observed for the unmodified or RGD-modified methacrylated alginate-based nanofibers [96]. ...
... Before the cross-linking the fiber diameters were between 185.5 ± 37 and 195.4 ± 23 nm, after cross-linking the fiber diameters were between 182.2 ± 36 and 190.4 ± 30 nm, but the PEO extraction lead to a diameter increase due to nanofiber swelling, ranging between 256.3 ± 43 and 297.9 ± 42 nm [96]. When this study used PEO/methacrylated heparin-, RGD-modified-, or unmodified methacrylated alginate-based nanofibers, it concluded that-by adding methacrylated heparin-the stress-strain curves are influenced, therefore making the elongation at break significantly lower and the tensile strength and Young's modulus significantly greater than those observed for the unmodified or RGD-modified methacrylated alginate-based nanofibers [96]. ...
Chronic wounds represent a major public health issue, with an extremely high cost worldwide. In healthy individuals, the wound healing process takes place in different stages: inflammation, cell proliferation (fibroblasts and keratinocytes of the dermis), and finally remodeling of the extracellular matrix (equilibrium between metalloproteinases and their inhibitors). In chronic wounds, the chronic inflammation favors exudate persistence and bacterial film has a special importance in the dynamics of chronic inflammation in wounds that do not heal. Recent advances in biopolymer-based materials for wound healing highlight the performance of specific alginate forms. An ideal wound dressing should be adherent to the wound surface and not to the wound bed, it should also be non-antigenic, biocompatible, semi-permeable, biodegradable, elastic but resistant, and cost-effective. It has to give protection against bacterial, infectious, mechanical, and thermal agents, to modulate the level of wound moisture, and to entrap and deliver drugs or other molecules This paper explores the roles of alginates in advanced wound-dressing forms with a particular emphasis on hydrogels, nanofibers networks, 3D-scaffolds or sponges entrapping fibroblasts, keratinocytes, or drugs to be released on the wound-bed. The latest research reports are presented and supported with in vitro and in vivo studies from the current literature.
... Rajam & Roopsingh [20,21] have shown that antimicrobial efficacy of photocrosslinkable copolyesters. Jeong et al. [22] synthesized biodegradable electrospun nanofibers composed of photo-crosslinkable alginate, which shows a great impact in wound soothing and tissue rejuvenation. Jeon et al. [23] developed the photocrosslinked HP-ALG hydrogel system, for the tissue engineering and regenerative medicine. ...
Four random copolyesters were prepared by the polycondensation reaction of diols namely 1,5-dihydroxyanthraquinone, 4,4′-oxybis(benzoic
acid) and variable chalcone diol. Four chalcone diols were produced by acid catalyzed Claisen-Schmidt reaction at room temperature.
These random copolyesters were elucidated by solubility tests and viscosity measurements. The FT-IR, 1H & 13C NMR techniques were
applied to establish the repeating units present in the copolyester backbone. Electrospinning method was employed to derive polyvinyl
chloride-copolyester-nanoclay composite nanofiber from tetrahydrofuran medium. Scanning electron microscopy (SEM) was utilized to
examine the morphology of the nanofibers. These composite nanofibers are expected to be a potential biomaterial of greater significance.
Keywords: Chalcone, Polyvinyl chloride, Copolyesters, Viscosity, Nanofibers.
... Some examples include adding a polymer such as polyethylene oxide (PEO) or polyvinyl alcohol (PVA) to facilitate the electrospinning process of other polymers [45][46][47][48], or to tailor characteristics of the scaffold [49,50], by adding a highly biocompatible polymer to a less biocompatible one to improve cell viability and proliferation [51][52][53], introducing a polymer such as chitosan to other polymers to enhance bioactivity, protein absorption and cell attachment on the scaffold [51,54], incorporating a polymer that can enhance cell proliferation and secrete collagen type I for better tissue regeneration [55], and blending two polymers possessing antibacterial activity to produce a scaffold with superior antibacterial effect [56]. It is worth noting that it is possible to extract a certain polymer from a blended mixture after electrospinning, if the presence of that certain polymer in the scaffold is undesirable or does not offer any therapeutic benefits [57,58]. ...
... The most common peptide to be covalently bonded to polymers in skin tissue engineering applications is the RGD peptide. RGD peptide (arginine-glycine-aspartate) is the cell binding sequence, and its incorporation in nanofibrous scaffolds enhance integrin-mediated cell adhesion and spreading, resulting in more cell proliferation compared to the scaffolds with no RGD peptides [45,58]. Moreover, covalent coupling of the peptide to the polymer does not affect the electrospinning process, and the peptide does not lose their bioactivity after the electrospinning process [45,58]. ...
... RGD peptide (arginine-glycine-aspartate) is the cell binding sequence, and its incorporation in nanofibrous scaffolds enhance integrin-mediated cell adhesion and spreading, resulting in more cell proliferation compared to the scaffolds with no RGD peptides [45,58]. Moreover, covalent coupling of the peptide to the polymer does not affect the electrospinning process, and the peptide does not lose their bioactivity after the electrospinning process [45,58]. ...
Skin is an essential protective organ in the body, and damage inflicted on its tissues can lead to serious problems if no proper care is given. Chronic skin wounds are the more serious type of wounds since they cannot heal normally on their own. Nanofibers are one of the promising solutions for better treatment of wounds, due to their availability, ability to mimic the skin extracellular matrix (ECM), and inability to transmit diseases unlike common skin grafts. Nanofibrous scaffolds are fabricated via different techniques including electrospinning, self-assembly, phase separation, and template synthesis. In this review article, we discuss the different ways of tailoring nanofibers, in order to produce an efficient wound healing scaffold for skin tissues. Parameters of nanofibers can be manipulated more easily and effectively with electrospinning than with other techniques. Electrospun nanofibers pass through different processing stages, and in each stage different techniques and manipulations can be conducted to improve the product. Pre-electrospinning treatment depends on the composition of the polymer solution that will be added to the electrospinner, and the electropinner setup itself can affect the produced fibers. Post-electrospinning treatment, which is the final modification that can be carried out in the fabrication process can also affect the properties of the produced nanofibers. Finally, the type of bioactive substance incorporated in the scaffold can help improve the bioactivity and efficiency of the scaffold. Therefore, this review provides an overview on the parameters affecting the electrospinning process of nanofibers, with emphasis on the most popular bioactive molecules incorporated within nanofibers for skin regeneration purposes.
... Wound healing is considered a complex process that involves a series of events, such as cell response, growth, and differentiation as well as a healing microenvironment and patient afflictions (age and illness) [69]. Therefore, the wound-care products must possess durability, non-toxicity, and flexiblility, while also being non-antigenic to facilitate wound repair. ...
Alginate has been a material of choice for a spectrum of applications, ranging from metal adsorption to wound dressing. Electrospinning has added a new dimension to polymeric materials, including alginate, which can be processed to their nanosize levels in order to afford unique nanostructured materials with fascinating properties. The resulting nanostructured materials often feature high porosity, stability, permeability, and a large surface-to-volume ratio. In the present review, recent trends on electrospun alginate nanofibers from over the past 10 years toward advanced applications are discussed. The application of electrospun alginate nanofibers in various fields such as bioremediation, scaffolds for skin tissue engineering, drug delivery, and sensors are also elucidated.
... Wound healing is considered a complex process that involves a series of events, such as cell response, growth, and differentiation as well as a healing microenvironment and patient afflictions (age and illness) [69]. Therefore, the wound-care products must possess durability, non-toxicity, and flexiblility, while also being non-antigenic to facilitate wound repair. ...
... aldehyde compounds such as glutaraldehyde are possible(Kyzioł, Michna, Moreno, Gamez, & Irusta, 2017;Vigani et al., 2018, Wang et al., 2019. Due to the toxicity of aldehyde groups and the possibility of replacing calcium cations with sodium ones in vivo, these fibers lose their stability and are not ideal for in vivo applications.Two other methods for increasing the stability of alginate nanofibers are converting them to the alginic acid nanofibers using acidic compounds such as trifluoroacetic acid or photo-crosslinking by photopolymerization process(Hajiali, Heredia-Guerrero, Liakos, Athanassiou, & Mele, 2015;Jeong, Jeon, Krebs, Hill, & Alsberg, 2012). Therefore, it can be expected that if the electrospun alginate nanofibers convert to insoluble alginic acid nanofibers, both the stability and biodegradability of nanofibers will be improved.Hajiali et al. showed that the nanofibers stabilized J o u r n a l P r e -p r o o f with this method are non-toxic against fibroblasts. ...
Alginate as a naturally-derived biomaterial with marine algae sources has gained much attention in both laboratorial and industrial applications due to its structural and chemical resemblance to extracellular matrix (ECM) as well as desirable properties like biocompatibility, biodegradability, processability and low cost. Electrospun alginate nanofibrous scaffolds have found wide applications in biomedical field such as tissue engineering, biomedicine and drug delivery systems. However, electrospinning of alginate is challenging due to the low solubility and high viscosity of high molecular weight alginate, high density of intra- and intermolecular hydrogen bonding, polyelectrolyte nature of aqueous solution and lack of appropriate organic solvent. The aim of this review is to summarize the challenges and obstacles in alginate electrospinning reported in the literature as well as the introduced solutions for them, in order to open new opportunities for more intended and successful investigations in the field.
